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· 2022
Abstract: Idiopathic pulmonary fibrosis (IPF) is a fatal disease with limited treatment options. In this study, we focus on the properties of airway basal cells (ABC) obtained from patients with IPF (IPF-ABC). Single cell RNA sequencing (scRNAseq) of bronchial brushes revealed extensive reprogramming of IPF-ABC towards a KRT17high PTENlow dedifferentiated cell type. In the 3D organoid model, compared to ABC obtained from healthy volunteers, IPF-ABC give rise to more bronchospheres, de novo bronchial structures resembling lung developmental processes, induce fibroblast proliferation and extracellular matrix deposition in co-culture. Intratracheal application of IPF-ABC into minimally injured lungs of Rag2−/− or NRG mice causes severe fibrosis, remodeling of the alveolar compartment, and formation of honeycomb cyst-like structures. Connectivity MAP analysis of scRNAseq of bronchial brushings suggested that gene expression changes in IPF-ABC can be reversed by SRC inhibition. After demonstrating enhanced SRC expression and activity in these cells, and in IPF lungs, we tested the effects of saracatinib, a potent SRC inhibitor previously studied in humans. We demonstrate that saracatinib modified in-vitro and in-vivo the profibrotic changes observed in our 3D culture system and novel mouse xenograft model
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A laboratory simulation of the spiral eddies viewed from the space shuttle Challenger on the STS 41-G mission was constructed. The construction allowed for collection of quantitative data coincident with the recording of any surface structure on polaroid film. A spiral flow was introduced into a test region, and the spiral nature of the flow verified by the plot of horizontal current velocity measurements. No manifestation of this flow, however, was evident on the water's surface. The unexpected results of the laboratory simulation provided the stimulus for a more in-depth study of the actual environmental conditions surrounding the presence of spiral eddies in the Levantine. Examination of the bathymetry revealed a direct relation between the generation and dissipation of spiral eddies, and the depth of the basin. Rotational motion of the eddies in this region is governed by the conservation of angular momentum.